The proposed work involves the development and exploitation of new methods for the study of cell kinetics in the intestinal epithelium. Methods have already been developed for the application of flow cytometry and these will be extended. Methods for rapid differential epithelial cell type counts will be perfected as will methods for the rapid assay of epithelial population size. These methods will be applied to several studies. First will be a test of the role of electrochemical gradients in modulating proliferation. The transmucosal potential will be fixed in vivo by voltage and later by current clamping. Changes in epithelial proliferation and differentiation will be monitored. Other studies involve the elucidation of the pattern of intercellular communication through gap junctions between crypt cells (studied by dye injection), the effects of immune complexes on proliferation and differentiation, the kinetics of circadian variations in proliferation and differentiation, a study of the controls over stem cell differentiation in the colon, and a study of the mode of cell migration in the villus epithelium.